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Baosheng Li M.D. Ph.D. Shandong Cancer Hospital, Department of Radiation Oncology

Comparison of SIB - I M RT and Conventional Accelerated Hyper-fractionated I M RT With Concurrent Cisplatin and Etoposide for Limited Disease SCLC. Baosheng Li M.D. Ph.D. Shandong Cancer Hospital, Department of Radiation Oncology. Disclosure. No conflict of interests to disclosure.

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Baosheng Li M.D. Ph.D. Shandong Cancer Hospital, Department of Radiation Oncology

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  1. Comparison of SIB-IMRT and Conventional Accelerated Hyper-fractionated IMRT With Concurrent Cisplatin and Etoposide for Limited Disease SCLC Baosheng Li M.D. Ph.D. Shandong Cancer Hospital, Department of Radiation Oncology

  2. Disclosure No conflict of interests to disclosure

  3. Background • At the time of diagnosis, 30%-40% of SCLC patients present with limited disease (LD). • SCLC is characterized by a rapid doubling time,high growth fraction, and early development of widespread metastases. • Patients with disease in excess of T1-2, N0 do not benefit from surgery. • Concurrent chemoradiotherapy represents the standard treatment for patients with LD-SCLC.

  4. Background • Accelerated hyper-fractionated radiotherapy (45Gy with 1.5Gy twice daily in 3 weeks) • Dose-escalated conventional radiotherapy (60-70Gy with 2Gy once daily in 6 to 7 weeks ) • Concurrent chemoradiotherapy have been documented as reliable schedules.

  5. RT in SCLC • 53.6%±3.3% SCLC patients need RT in every stage in the disease • 45.4%±4.3% SCLC patients in the initial treatment • 8.2%±1.5% SCLC patients later for recurrence or progression • Local failures occur in approximately one third of patients and the outcome is still poor.

  6. RTOG 97-12 Komaki R, et al. IJROBP. 62,342-350, 2005

  7. RTOG 97-12 Lg Field (1.8 Gy/Fx) Boost (1.8Gy Bid) Total Dose x (off cord) Wk 1 2 3 4 5

  8. RTOG 0239 • RT compliance rate: 95 % • Objective response: • CR: 41%, PR: 39% • 2Y OS: 36.6 % Severe hematopoietic toxicity was as high as 90% ( 15 grade 3 and 49 grade 4).

  9. NCCTG 95-20-53 • Protocol: • 6 cycles of etoposide and cisplatin . • Cycles 4 and 5 included concurrent higher dose • TRT (30Gy/20 twice daily fractions, a 2-week break, and another 30Gy/20 twice daily fractions). Schild SE,et al. J Clin Oncol 2007, 25: 3124-3129.

  10. Results • A total of 76 assessable patients enrolled. • 5-year OSrate: 24%. • The locoregional failure remained a problem and grade 3 or grade (3+) toxicities were as high as 97%.

  11. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer Sun jm,et al. Ann Oncol. 2013;24(8):2088-92

  12. Results: 222 patients were randomly assigned • early TRT Late TRT P-value • CR 36% 38% >0.05 • Median OS 24.1 26.8 >0.05 • Median PFS 12.4 11.2 >0.05 • Meutropenic fever 21.6% 10.2% 0.02 • Conclusion: TRT starting in the third cycle of chemotherapy seemed to be noninferior to early TRT, and had a more favorable profile with regard to neutropenic fever.

  13. Purpose Ourretrospective study was to compare toxicities, disease control and survival outcomes for LD-SCLC treated with simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) versus conventional accelerated hyper-fractionated radiotherapy.

  14. METHODS

  15. Patient Characteristics

  16. Chemotherapy • Two cycles chemotherapy before TRT with EP regimen (etoposide 100mg/m2 day 1-5, and cisplatin 25mg/m2 day 1-3, 21 days per cycle) were delivered. • Then adjuvant chemotherapy were administered after completion of thoracic radiotherapy. Chemotherapy was administered every 3 weeks. • A total of 4-6 cycles were administered.

  17. SIB-IMRT protocols • GTV: including the residual primary tumor and involved lymph nodes after induction chemotherapy. • TDF: 1.9Gy/f @ 30f in 3 weeks, 5 days a week. • CTV: defined by expanding GTV with a 0.5 cm margin and involved lymph node region. • TDF: 1.7Gy/f @ 30f in 3 weeks , 5 days a week. • PTV: defined by expanding CTV with a 0.5 cm margin. • TDF: 1.5Gy/f @ 30f in 3 weeks , 5 days a week.

  18. SIB-IMRT

  19. Conventional Accelerated Hyper-fractionated RadiotherapyProtocols • The targets were defined as the same as SIB-IMRT. • TDF:1.5Gy/f @ 30f in 3 weeks , 5 days a week to PTV.

  20. Organs at risk • Lung：mean lung dose < 20Gy, lung V20 < 33%； • spinal cord : Dmax≤41Gy; • Heart：mean heart dose < 30Gy，V40<46%； • Esophagus：mean esophagus dose < 34 Gy, • V35 < 50% .

  21. Prophylactic cranial irradiation • Patients who achieved CR or nCR were administered PCI (25 Gy in 10 fractions to the entire brain) within 4 weeks after completion of all chemotherapy.

  22. Results

  23. Total lungs

  24. Toxicity

  25. Treatment response

  26. Survival

  27. OS P = 0.165

  28. PFS P = 0.077

  29. LRFS P = 0.093

  30. Conclusions • Comparing with conventional accelerated hyper-fractionated RT, SIB-IMRT for limited Disease SCLC was feasible and had the potency of improving local regional recurrence. However, the toxicity was still higher.

  31. Acknowledgements • Dr. Dan Han • Dr. Tao Zhou • Dr. Zhongtang Wang • Dr. Hongsheng Li • Prof. Yong Yin • Associate Prof. Jian zhu

  32. Thank you !

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